Systems and methods for making gelatin shunts

ABSTRACT

The invention generally relates to systems and methods for making gelatin shunts. In certain embodiments, the invention provides methods that may involve moving a wire through a bath including a bottom layer of liquid gelatin and a top layer of water, thereby coating the wire with gelatin, moving the gelatin coated wire through an aperture, and drying the gelatin on the wire in a humidity controlled space, thereby manufacturing a gelatin shunt. In other embodiments, the invention provides systems that may include a motor, a wire operably coupled to the motor for movement of the wire, a temperature controllable bath, an aperture plate situated in a top portion of the bath, and an ultrasonic fogger, in which the system is configured such that the wire moves through the bath, through the aperture plate, and into the ultrasonic fogger.

FIELD OF THE INVENTION

The invention generally relates to systems and methods for makinggelatin shunts.

BACKGROUND

Glaucoma is a disease of the eye that affects millions of people.Glaucoma is associated with an increase in intraocular pressureresulting either from a failure of a drainage system of an eye toadequately remove aqueous humor from an anterior chamber of the eye oroverproduction of aqueous humor by a ciliary body in the eye. Build-upof aqueous humor and resulting intraocular pressure may result inirreversible damage to the optic nerve and the retina, which may lead toirreversible retinal damage and blindness.

Glaucoma may be treated in a number of different ways. One manner oftreatment involves delivery of drugs such as beta-blockers orprostaglandins to the eye to either reduce production of aqueous humoror increase flow of aqueous humor from an anterior chamber of the eye.Glaucoma may also be treated by surgical intervention that involvesplacing a shunt in the eye to result in production of fluid flowpathways between an anterior chamber of an eye and various structures ofthe eye involved in aqueous humor drainage (e.g., Schlemm's canal, thesclera, or the subconjunctival space). Such fluid flow pathways allowfor aqueous humor to exit the anterior chamber.

A problem with implantable shunts is that they are composed of a rigidmaterial, e.g., stainless steel, that does not allow the shunt to reactto movement of tissue surrounding the eye. Consequently, existing shuntshave a tendency to move after implantation, affecting ability of theshunt to conduct fluid away from the anterior chamber of the eye. Toprevent movement of the shunt after implantation, certain shunts areheld in place in the eye by an anchor that extends from a body of theshunt and interacts with the surrounding tissue. Such anchors result inirritation and inflammation of the surrounding tissue. Further,implanting a rigid shunt may result in the shunt causing blunt traumaupon insertion into an eye, such as producing a cyclodialysis cleft, orseparation of the ciliary body from the scleral spur, creating hypotonyby allowing the uncontrolled escape of aqueous humor through the cleftinto the suprachoroidal space.

To address the problems associated with shunts made of rigid material,people have begun to make shunts from flexible material, such asgelatin. See for example, Yu et al. (U.S. Pat. No. 6,544,249 and U.S.patent application publication number 2008/0108933). Gelatin shunts maybe reactive to pressure, and thus can be implanted without the use ofanchors. Consequently, gelatin shunts will maintain fluid flow away foran anterior chamber of the eye after implantation without causingirritation or inflammation to the tissue surrounding the eye.Additionally, the flexibility of a gelatin shunt prevents it fromcausing blunt trauma upon insertion into an eye, and thus reduces oreliminates the risk of producing a cyclodialysis cleft.

However, there are numerous issues associated with making gelatinshunts. For example, it is difficult to control and manipulate liquidgelatin, which is important in order to produce a gelatin shunt with auniform cross-section and uniform shape along a length of the implant.Additionally, there are challenges associated with the drying processthat also make it difficult to produce a gelatin shunt with a uniformcross-section and uniform shape along a length of the implant.

SUMMARY

The invention generally provides systems and methods for making gelatinshunts. Particularly, systems and methods of the invention address andsolve the above described problems with manufacturing gelatin shunts.

Certain aspects of the invention address the problems of controlling andmanipulating liquid gelatin. The invention recognizes that simplyrouting a wire through a temperature controlled gelatin bath is notsufficient to produce a gelatin shunt with a uniform cross-section anduniform shape along a length of the implant. Heated gelatin alone formsa skin layer on top of the gelatin. Pulling a wire through a gelatinbath alone results in the wire passing through the skin layer, whichmakes it impractical to control the gelatin uptake on the wire. Theinvention solves this aspect of the problem by adding a water layer ontop of the gelatin. The water layer eliminates the skin effect, andallows for production of a uniform cone of gelatin upon pulling a wirethrough the gelatin and then the water layer. Where the gelatin coneintersects the water-air boundary, a spot forms. This spot is exposed toair, and gelatin from this spot is taken up the wire.

However, the invention also recognizes that more gelatin reaches the topof the water than can be taken up by the wire. This results in cast-off,which renders the cone, and thus the spot at the boundary layer,unstable, i.e., the gelatin deposit is inconsistent in diameter. Tosolve this aspect of the problem, the systems and methods of theinvention use a plate having an aperture, which aperture controls thegelatin spot. The plate having the aperture is situated in the waterlayer, and with the aperture plate in place, the cone of gelatin thatfeeds the spot is consistent and yields a uniform uptake of gelatin ontothe wire.

Other aspects of the invention address the problems associated with thedrying process that also make it difficult to produce a gelatin shuntwith a uniform cross-section and uniform shape along a length of theimplant. As the water evaporates from the gelatin on the wire, thegelatin shrinks in diameter. However, the wire constrains the gelatinfrom shrinking axially. If humidity is left uncontrolled, an outer skinof the gelatin dries and hardens before the gelatin has completedshrinking. This results in non uniform cross sections and shapes alongthe implant length. The invention recognizes that drying the gelatin onthe wire in a humidity controlled space produces a uniform implant alongthe length of the wire. One manner by which this is accomplishedinvolves immersing the gelatin in an ultrasonic fog that keeps the outerskin of the gelatin hydrated as the internal volume of the gelatinshrinks.

Systems and methods of the invention incorporate these solutions to theabove described problems associated with manufacturing a gelatin shunt.Methods of the invention may involve moving a wire through a bathincluding a bottom layer of liquid gelatin and a top layer of water,thereby coating the wire with gelatin, moving the gelatin coated wirethrough an aperture, and drying the gelatin on the wire in a humiditycontrolled space, thereby manufacturing a gelatin shunt. The dried shuntincludes a uniform shape and a uniform cross-section.

Movement of the wire may be controlled manually or mechanically. Incertain embodiments, the moving wire is mechanically controlled, by forexample, by a stepper motor.

Any method for controlling humidity may be used with methods of theinvention. In particular embodiments, the humidity is controlled bydrying in the presence of an ultrasonic water fog. The aperture isgenerally located in the water layer, and the wire is preferably movedvertically through the bath, such that the gelatin coated wire isvertical during the drying step. In certain embodiments, themanufactured shunt is sized and dimensioned to be an intraocular shunt.

In certain embodiments, the liquid gelatin may include a drug, and thusproduces shunts that may be coated or impregnated with at least onepharmaceutical and/or biological agent or a combination thereof. Anypharmaceutical and/or biological agent or combination thereof may beused with shunts of the invention. The pharmaceutical and/or biologicalagent may be released over a short period of time (e.g., seconds) or maybe released over longer periods of time (e.g., days, weeks, months, oreven years). Exemplary agents include anti-mitotic pharmaceuticals suchas Mitomycin-C or 5-Fluorouracil, anti-VEGF (such as Lucintes, Macugen,Avastin, VEGF or steroids). Exemplary agents are shown in Darouiche(U.S. Pat. Nos. 7,790,183; 6,719,991; 6,558,686; 6,162,487; 5,902,283;5,853,745; and 5,624,704) and Yu et al. (U.S. patent application serialnumber 2008/0108933). The content of each of these references isincorporated by reference herein its entirety.

Systems of the invention may include a motor, a wire operably coupled tothe motor for movement of the wire, a temperature controllable bath, anaperture plate situated in a top portion of the bath, and an ultrasonicfogger, the system being configured such that the wire moves through thebath, through the aperture plate, and into the ultrasonic fogger.Generally, the wire initially moves down toward a bottom of the bath andthen turns to move vertically out of the bath. From there, the wiremoves through the aperture plate, and then the wire moves verticallythrough the ultrasonic fogger.

Systems of the invention may also include a first camera positioned toview the wire as it moves through the aperture plate. Systems of theinvention may also further include a second camera that includessoftware to measure the gelatin coated wire as it passes into thefogger.

The bath may be filled with liquid gelatin and water. The liquid gelatinfills a bottom layer of the bath and the water fills a top layer ofbath. In certain embodiments, the liquid gelatin includes a drug.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic shows an embodiment of a system of the invention.

FIG. 2 is a schematic showing a magnified view of FIG. 1, focusing onthe wheels that carry the wire.

FIG. 3 is an image of the aperture plate with a wire running through theaperture.

FIG. 4 shows the images captured by the first and second camera as thewire emerges from the aperture in the aperture plate.

FIG. 5 is a schematic showing the wire being pulled through the gelatinand water layers and through the aperture in the aperture plate.

FIG. 6 is a schematic showing a magnified view of a gelatin coneinteracting with the aperture plate as the wire moves through theaperture plate.

FIG. 7 is a schematic showing an exploded view of a spool.

FIG. 8 is a schematic showing the final assembled spool.

DETAILED DESCRIPTION

FIG. 1 shows an embodiment of a system 100 of the invention formanufacturing a gelatin shunt. Device 100 includes a base 101 and avertically extending shaft 102. There is a bath 103 at an the junctionof the base 101 and the shaft 102, such that the shaft 102 is alignedwith the bath 103. The bath 103 can be any vessel configured to hold aliquid. In systems of the invention, the bath 103 holds the liquidgelatin and the water. The bath is operably connected to a temperaturecontrol unit 104. The temperature control unit 104 regulates thetemperature of the bath 103, and any liquids within the bath 103. Formaking a shunt, the bath is maintained at about 55° C.

In particular embodiments, the bath 103 is a jacketed flask and thetemperature control unit 104 is a water circulator with a heatingcomponent. The heater of the temperature control unit is set to aparticular temperature, for example 55° C., which heats the water in thewater circulator to the set temperature. The heated water is thencirculated by the water circulator to the jacked flask, which heats theflask, and its contents, to the temperature defined by the temperaturecontrol unit. Generally, the water level in the jacketed flask will beabove the level of the gelatin inside the flask.

To the top of the bath 103 is affixed an aperture plate 105, i.e., aplate having an aperture 106 therethrough. The plate 105 is affixed tothe bath 103 such that the aperture 106 is aligned with the shaft 102.An exemplary shaped aperture plate 105 is shown in FIG. 3. In thisfigure, the plate 105 has a base portion and a protruding portionaffixed to the base. The aperture runs through the base and through theprotruding portion.

System 100 includes a plurality of wheels 107. The wheels 107 support awire 108 and are arranged in a path that the wire 108 will travel. FIG.2 is a magnified view of the system 100 shown in FIG. 1. FIG. 2 bettershows the positioning of wheels 107 and the path of travel of wire 108.Wheel 107 a is mounted approximately half way up the shaft 102. Theexact position of wheel 107 a on shaft 102 is not important and otherpositions of wheel 107 a are envisioned for the systems of theinvention. Wheel 107 b is mounted on a support near the base 101 and ispositioned to be directly below wheel 107 a. Although, such exactpositioning is not critical and wheel 107 b may be placed in otherplaces along the base. Wheel 107 c is mounted at a top right edge of thebath 103. Wheel 107 d is mounted at a bottom of bath 103. Wheel 107 d ismounted such that it is in alignment with aperture 106 of aperture plate105 and shaft 102. Wheel 107 e is positioned at the top of shaft 102.The exact position of wheel 107 e on shaft 102 is not important andother positions of wheel 107 e are envisioned for the systems of theinvention. Wheel 107 f is mounted on a support near the base 101. Wheel107 f is operably coupled to stepper motor 109. An exemplary steppermotor is commercially available from Automation Direct (Cumming, Ga.).

The wheels 107 are arranged such that when wire 108 is mounted on wheels107, the wheels provide a constant tension for wire 108. Wire 108 isspooled on wheel 107 a. Wire 108 is then run under wheel 107 b, overwheel 107 c, under wheel 107 d, over wheel 107 e, and spools again ontowheel 107 f. The arrangement provides that wire 108 travels down intothe base of bath 103, and makes a turn at the base of bath 103, suchthat after the turn, wire 108 travels vertically up through the bath103, through the aperture 106 of the aperture plate 105, and verticallyup the length of the shaft 102 to wheel 107 e.

Stepper motor 109 in connection with wheel 107 f drives movement of wire108 and controls the speed at which wire 108 travels. The thickness ofthe walls of the formed shunt will depend on the speed at which the wire108 is traveling. Increasing the pull speed will increase the diameterof the shunt, while decreasing the pull speed will decrease the diameterof the shunt. Stepper motor 109 is controlled by computer 114 andpowered by DC power supply 115.

Wire 108 is preferably stainless steel, which may optionally be coatedwith a biocompatible, lubricious material such aspolytetrafluoroethylene (Teflon). The coating helps in removing thedried gelatin shunt from the wire 108. The gauge of the wire will dependon the desired inner diameter of the shunt being produced. Generally,wires are used that produce a shunt having an inner diameter fromapproximately 10 μm to approximately 250 μm, preferably from about 40 μmto about 200 μm.

System 100 may include at least one camera for real time monitoring ofthe manufacturing of the shunt. FIGS. 1-2 show an embodiment thatincludes two cameras 110 and 111. Camera 110 monitors the wire 108 atthe point that it is emerging from the aperture 106. Camera 111 is ahigh magnification camera that includes measurement software to allowfor real time measurement of the thickness and diameter of the gelatincoating the wire 108 as it emerges from the aperture 106. Exemplarycameras are DINO-LITE cameras, commercially available from (AnMoElectronics Corporation, Torrance, Calif.). FIG. 4 shows the imagescaptured by cameras 110 and 111. The top image, is the image produced bycamera 111, and the bottom image is the image produced by camera 110).Cameras 110 and 111 are operably coupled to computer 114, which controlsthe cameras.

System 100 also includes an ultrasonic fogger 112 coupled to a tube 113.The tube 113 runs most of the length of the shaft 102, extending fromthe top of the shaft 102 down to the top camera 111. The tube 113 ispositioned such that the wire 108 pass into the tube 113 upon emergingfrom the aperture 106. The fogger 112 is positioned such that theproduced fog enters the tube 113. The fog produced by the fogger 112keeps the outer skin of the gelatin hydrated as the internal volume ofthe gelatin shrinks. An exemplary fogger is commercially available fromExo-terra (Mansfield, Mass.).

To make the gelatin shunt, the bath 103 is pre-heated to a temperatureof about 55° C. During the pre-heating, the liquid gelatin 116 is made.In a certain embodiment, the gelatin used for making the shunt is knownas gelatin Type B from bovine skin. An exemplary gelatin is PB Leinergelatin from bovine skin, Type B, 225 Bloom, USP. Another material thatmay be used in the making of the shunt is a gelatin Type A from porcineskin, also available from Sigma Chemical. Such gelatin is available fromSigma Chemical Company of St. Louis, Mo. under Code G-9382. Still othersuitable gelatins include bovine bone gelatin, porcine bone gelatin andhuman-derived gelatins. In addition to gelatins, the flexible portionmay be made of hydroxypropyl methycellulose (HPMC), collagen, polylacticacid, polylglycolic acid, hyaluronic acid and glycosaminoglycans.

In an exemplary protocol, the gelatin solution is typically prepared bydissolving a gelatin powder in de-ionized water or sterile water forinjection and placing the dissolved gelatin in a water bath at atemperature of approximately 55° C. with thorough mixing to ensurecomplete dissolution of the gelatin. In one embodiment, the ratio ofsolid gelatin to water is approximately 10% to 50% gelatin by weight to50% to 90% by weight of water. In an embodiment, the gelatin solutionincludes approximately 40% by weight, gelatin dissolved in water. Theresulting gelatin solution should be devoid of air bubbles and has aviscosity that is between approximately 200-500 cp and more particularlybetween approximately 260 and 410 cp (centipoise).

FIGS. 5 and 6 illustrate the process of the gelatin 116 being taken upthe wire 108. Once prepared, the liquid gelatin 116 is poured into bath103 that has been pre-heated to 55° C., thus maintaining the liquidgelatin at 55° C. After the gelatin 116 has been poured into the bath103, a water layer 117 is added on top of the gelatin layer 116. Thewater envelops the aperture plate 105 such that a top surface of theplate 105 is submerged about 1 mm below the surface of water 117. Thebottom of the plate 105 is positioned so that it does not touch thegelatin layer 116. Powered by stepper motor 109, the wire 108 is pulleddown into the base of the bath 103 and then turns vertically up throughthe gelatin layer 116, the water layer 117, and the aperture 106 in theaperture plate 105. In this manner, the wire 108 becomes coated withgelatin 116 as it passes through the gelatin layer 116. Upon pulling thegelatin 116 through the water layer 117, a uniform cone 118 of gelatin116 forms. Where the cone 118 intersects the water-air boundary, a spotforms. The cone 118 feeds into the aperture 106 in the aperture plate105. The aperture 106 controls the gelatin 116 and the spot, such thatthe cone 118 of gelatin 116 that feeds the spot is consistent and yieldsa uniform uptake of gelatin 116 onto the wire 108.

The wire 108 then advances past cameras 110 and 111, which provide areal-time check of the thickness of the gelatin 116 that is being takenup the wire 108. Feedback from the camera can be used to adjust thespeed of the wire 108, thus adjusting the thickness of the gelatin 116.Increasing the pull speed will increase the diameter of the shunt, whiledecreasing the pull speed will decrease the diameter of the shunt.

After passing the cameras, the gelatin coated wire moves into tube 113that is already being supplied with fog from fogger 112. The wire 108 isadvanced until the wet gelatin 116 reaches the wheel 107 e at the top ofthe shaft 102. The gelatin 116 on the wire 108 becomes immersed in thefog from fogger 112. The fogger is run for approximately 5-10 minutesafter the gelatin coated wire enters the fogger. The fogger is turnedoff and the gelatin is allowed to dry. Having the outer skin of thegelatin 116 in a humidity controlled environment, keeps the skin of thegelatin 116 hydrated as an internal volume of the gelatin 116 shrinks.In this manner, a uniform implant is produced along the length of thewire 108.

The wire 108 is then cut below wheel 107 e and above the top camera 111,using for example, stainless steel surgical sheers. The wire is cut intosections using the stainless steel surgical sheers to produce sectionsof a desired length. At this point, a cross-linking procedure can beperformed on the gelatin. In one embodiment, the gelatin may becross-linked by dipping the wire sections (with gelatin thereon) intothe 25% glutaraldehyde solution, at pH of approximately 7.0-7.8 and morepreferably approximately 7.35-7.44 at room temperature for at least 4hours and preferably between approximately 10 to 36 hours, depending onthe degree of cross-linking desired. In one embodiment, the gelatin iscontacted with a cross-linking agent such as gluteraldehyde for at leastapproximately 16 hours. Cross-linking can also be accelerated when it isperformed a high temperatures. It is believed that the degree ofcross-linking is proportional to the bioabsorption time of the shuntonce implanted. In general, the more cross-linking, the longer thesurvival of the shunt in the body.

The residual glutaraldehyde or other cross-linking agent is removed fromthe gelatin by soaking the tubes in a volume of sterile water forinjection. The water may optionally be replaced at regular intervals,circulated or re-circulated to accelerate diffusion of the unboundglutaraldehyde from the gelatin. The gelatin is washed for a period of afew hours to a period of a few months with the ideal time being 3-14days. The now cross-linked gelatin may then be dried (cured) at ambienttemperature for a selected period of time. It has been observed that adrying period of approximately 48-96 hours and more typically 3 days(i.e., 72 hours) may be preferred for the formation of the cross-linkedgelatin.

Where a cross-linking agent is used, it may be desirable to include aquenching agent. Quenching agents remove unbound molecules of thecross-linking agent from the gelatin. In certain cases, removing thecross-linking agent may reduce the potential toxicity to a patient iftoo much of the cross-linking agent is released from the gelatin. Incertain embodiments, the gelatin is contacted with the quenching agentafter the cross-linking treatment and, may be included with thewashing/rinsing solution. Examples of quenching agents include glycineor sodium borohydride.

In certain embodiments, drug coated/drug impregnated shunts areproduced. Shunts may be coated or impregnated with at least onepharmaceutical and/or biological agent or a combination thereof. Anypharmaceutical and/or biological agent or combination thereof may beused with shunts of the invention. The pharmaceutical and/or biologicalagent may be released over a short period of time (e.g., seconds) or maybe released over longer periods of time (e.g., days, weeks, months, oreven years). Exemplary agents include anti-mitotic pharmaceuticals suchas Mitomycin-C or 5-Fluorouracil, anti-VEGF (such as Lucintes, Macugen,Avastin, VEGF or steroids). Exemplary agents are shown in Darouiche(U.S. Pat. Nos. 7,790,183; 6,719,991; 6,558,686; 6,162,487; 5,902,283;5,853,745; and 5,624,704) and Yu et al. (U.S. patent application serialnumber 2008/0108933). The content of each of these references isincorporated by reference herein its entirety.

In certain embodiments, an implant is produced with a thin layer of druginfused gelatin on an inside of the shunt. The thin inner layer willdissolve over time, thus delivering the drug.

To produce such a shunt, the wire is pulled through a gelatin solutionthat has been infused with a drug to deposit a thin wall (e.g., 3-20 μm)of drug-infused gelatin on the wire. Alternatively, the wire is pulledthrough a gelatin solution that does not include a drug and the gelatinis instead soaked in the drug after it is pulled on the wire. In eithercase, the drug infused gelatin is then subjected to crosslinking with acontrolled glutaraldehyde concentration for a controlled time to effecta non-permanent crosslinking that dissolves over time in tissue. Oncethis drug infused gelatin has been produced, the drug-infused gelatin isthen pulled through the standard gelatin bath to coat the drug infusedgelatin with a layer of gelatin that does not include a drug. Thisproduces he final diameter of the shunt. The drug free layer of gelatinis then permanently crosslinked, thus producing a shunt with a thinlayer of drug infused gelatin on an inside of the shunt.

In other embodiments, an implant is produced with a thin layer of druginfused gelatin on an outside of the shunt. The thin inner layer willdissolve over time, thus delivering the drug. To produce such a shunt,the wire is pulled through the standard gelatin solution in the bath toa diameter of about 3-50 the wire is pulled through the standard gelatinsolution in the bath to a diameter of about 3-50 μm smaller than thedesired diameter of the final implant. This layer is permanentlycrosslinked. The gelatin coated wire is then pulled through a druginfused gelatin solution to deposit a thin wall (e.g., 3-50 μm) onto thegelatin coated wire. Alternatively, the wire is pulled through a gelatinsolution that does not include a drug and the gelatin is instead soakedin the drug after it is pulled on the wire. In either case, the druginfused gelatin is then subjected to crosslinking with a controlledglutaraldehyde concentration for a controlled time to effect anon-permanent crosslinking that dissolves over time in tissue.

Incorporation by Reference

References and citations to other documents, such as patents, patentapplications, patent publications, journals, books, papers, webcontents, have been made throughout this disclosure. All such documentsare hereby incorporated herein by reference in their entirety for allpurposes.

Equivalents

The invention may be embodied in other specific forms without departingfrom the spirit or essential characteristics thereof. The foregoingembodiments are therefore to be considered in all respects illustrativerather than limiting on the invention described herein. Scope of theinvention is thus indicated by the appended claims rather than by theforegoing description, and all changes which come within the meaning andrange of equivalency of the claims are therefore intended to be embracedtherein.

EXAMPLES Example 1 Gelatin Preparation

Into a 600 mL beaker was added 98±1 grams of porcine gelatin. An amountof about 172±1 grams of USP sterile water was measured and poured intothe beaker containing the porcine gelatin. The beaker was sealed withparafilm, and the covered beaker was placed in a water bath at 55±1° C.for a minimum of 8 hours (maximum 36 hours). Ensure water level ishigher than mixture in beaker. The lid of the water bath was checked toensure that it was closed and after the minimum time period had elapsed,the beaker was removed from bath. The beaker was visually observed toverify that all gelatin in the mixture was dissolved and that mixtureappeared homogeneous.

Example 2 Gelatin Transfer

The water circulator was checked to make sure that it was at asufficient level (between the high and low marks). The circulator wasset and run at 40.5° C. and allowed to come to temperature beforeproceeding to the next step. The gelatin mixture from Example 1 waspoured into the jacketed beaker on a fixture so that the meniscus wasabout 20 mm from the top. Within 1 minute of adding the gelatin mixture,60 cc's of USP sterile water was added above the gelatin surface using asyringe. The water was added slowly so as not to disturb the gelatin.The mixture was allowed to settle for minimum 30 min.

Example 3 System Set-Up

A spool was assembled onto an axle using parts as shown in FIG. 7. Thefinal assembled spool is shown in FIG. 8. The M6 screw (Item 8) wasfinger tightened, and pinch bolt (Item 7) was fastened onto the mount.In order to increase the friction on the spool, the M6 screw (Item 8)was advanced approximately a ¼ turn. The wire was then threaded onto thespool, and the spool was slid up the shaft. The spindle assembly waslowered into the gelatin mixture, about 5 mm from the bottom of flask.The aperture plate was lowered into the water layer under a top surfacewas submerged about 1 mm below the surface of water. The bottom surfaceof the aperture plate was above the gelatin layer.

The first and second cameras were positioned on the shaft so as toproperly view the wire as it emerged from the aperture in the apertureplate. The tube of the fogger assembly was lowered over the shaft untila bottom of the tube is positioned just above the second camera. In thisposition, a top of the tube was approximately 2 inches above the upperwheel on the shaft. The fogger was started, and the volume and velocityon the fogger was adjusted until the fog was barely visible flowing atthe bottom of the tube. The computer was initiated and the imagesproduced by the camera were checked to ensure proper positioning of thecameras. The cameras were focused until edges of the wire had sharpcontrast.

Example 4 Shunt Manufacturing

The computer was used to initiate the stepper motor and begin pullingthe wire. The initial pull speed was 8,000 rpm. The aperture was checkedfor dry gelatin, and any dried gelatin was cleared by grasping the wireabove the top camera using a gloved hand and swirling the wire aroundlightly for a few seconds while monitoring the aperture cameras. Theconcentration of the gelatin on the wire was fine tuned by monitoringthe cameras. Turning the X-axis stage micrometer in the clockwisedirection moved the wire to the right relative to the gelatin. Turningthe Y-axis stage micrometer in the clockwise direction moved the wire tothe left relative to the gelatin. Active measures of the gelatinthickness on the wire were taken. The total diameter of the gelatin inboth the X and Y views was measured. The relative wall thickness of thegelatin on each side of the wire in both the X and Y views was obtainedby measuring from the left edge of the gelatin to the left edge of thewire and from the right edge of the gelatin to the right edge of thewire. The pull speed was adjusted to achieve a target wet diameter ofthe gelatin.

Once the target wet diameter was achieved, the fixture was run untilgelatin reached the upper wheel at the top of the shaft. The movement ofthe wire was stopped at this point. After terminating the movement ofthe wire, the fog from the fogger was allowed to continue to flow overthe wire for a minimum of 5 additional minutes. After five minutes, thefogger was turned off and the gelatin was allowed to dry for a minimumof 3 additional minutes. The wire was then cut below the upper wheel andabove the top camera using stainless steel surgical shears. The cut wirewas then subsequently cut into 4-4.25 inch sections using stainlesssteel surgical shears and prepared for crosslinking. The individualsections were crosslinked. The shunts were then cut to a desired length(e.g., 2-20 mm), and each shunt was removed from the wire.

What is claimed is:
 1. A method for manufacturing a gelatin shunt, themethod comprising: moving a wire through a bath comprising a bottomlayer of liquid gelatin and a top layer of water, thereby coating thewire with gelatin; moving the gelatin coated wire through an aperture;and drying the gelatin on the wire in a humidity controlled space,thereby manufacturing a gelatin shunt.
 2. The method according to claim1, wherein the dried shunt comprises a uniform shape and a uniformcross-section.
 3. The method according to claim 1, wherein the liquidgelatin comprises a drug.
 4. The method according to claim 1, whereinthe moving wire is mechanically controlled.
 5. The method according toclaim 1, wherein the humidity is controlled by drying in the presence ofan ultrasonic water fog.
 6. The method according to claim 1, wherein theaperture is in the water layer.
 7. The method according to claim 1,wherein the wire is moved vertically through the bath.
 8. The methodaccording to claim 1, wherein the gelatin coated wire is vertical duringthe drying step.
 9. The method according to claim 1, wherein themanufactured shunt is sized and dimensioned to be an intraocular shunt.10. A system for manufacturing a gelatin shunt, the system comprising: amotor; a wire operably coupled to the motor for movement of the wire; atemperature controllable bath; an aperture plate situated in a topportion of the bath; and an ultrasonic fogger; wherein the system isconfigured such that the wire moves through the bath, through theaperture plate, and into the ultrasonic fogger.
 11. The system accordingto claim 10, wherein the wire initially moves down toward a bottom ofthe bath and then turns to move vertically out of the bath.
 12. Thesystem according to claim 11, wherein the wire moves through theaperture plate.
 13. The system according to claim 12, wherein the wiremoves vertically through the ultrasonic fogger.
 14. The system accordingto claim 13, further comprising a first camera positioned to view thewire as it moves through the aperture plate.
 15. The system according toclaim 14, further comprising a second camera that comprises software tomeasure the gelatin coated wire as it passes into the fogger.
 16. Thesystem according to claim 15, further comprising liquid gelatin fillinga bottom layer of the bath and water filling a top layer of bath. 17.The system according to claim 16, wherein the liquid gelatin comprises adrug.
 18. The system according to claim 10, wherein the shunt is anintraocular shunt.